Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.
Epidermal growth factor receptor (EGFR) mediated mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was isolated as invasion-metastasis related factor in pancreatic cancer in our previous studies.
Cetuximab (IMC-C225, Erbitux(TM)), a monoclonal EGFR antibody, has been FDA approved for the therapy of irinotecan resistant colorectal cancer and has been tested for pancreatic cancer.
In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.
The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer.
The recent elucidation both of the mechanisms involved in pancreatic cancer carcinogenesis and the related molecular events, has led to several distinct therapeutic advances, including many novel target agents, such as monoclonal antibodies against EGFR, EGFR-tyrosine kinase inhibitors, monoclonal antibody against VEGF, farnesyl transferase inhibitors, matrix metalloproteinase inhibitors, COX 2 inhibitors, and the development of gene therapy to target pancreatic cancer.
The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy.
Quantitative RT-PCR analysis revealed that HRGs as well as its signaling ErbB receptors were present in 4 of 4 human pancreatic cancer cell lines (PCCL).
Synergistic antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, with gemcitabine and ionizing radiation against pancreatic cancer.
Therefore, the strategies targeting EGFR, Akt, NF-kappaB, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer.
In addition, the data support the efficacy of combined epidermal growth factor receptor and MAPK inhibitors in biliary and pancreatic cancers, providing the basis to test this combination in the clinic.
Allele-specific EGFR intron 1 lengths were analyzed in 30 microdissected pancreatic cancer surgical specimens, matched peripheral blood samples, and 9 pancreatic cancer cell lines treated with erlotinib.
Tyrosine kinase receptors such as members of the epidermal growth factor receptor family and their respective ligands are frequently overexpressed in pancreatic cancer as well as in chronic pancreatitis.
We also observed signaling pathways unique to specific types of cancers such as the inverse relationship between p16ink and Rb, and the EGFR mediated pathway activation characteristic of pancreatic cancers.
EGFR gene copy number was analyzed by fluorescence in situ hybridization in nine pancreatic cancer cell lines and 31 pancreatic cancer surgical specimens.
By a systematic study across low passage pancreatic cancer cell lines and mice carrying pancreatic cancer xenografts, we have demonstrated activated epidermal growth factor receptor as an attractive candidate for targeted therapy in a subset of pancreatic cancers.